المؤلفون: Robin Kristófi, Johan Bodegard, Viveca Ritsinger, Marcus Thuresson, David Nathanson, Thomas Nyström, Anna Norhammar, Jan W. Eriksson

المصدر: Cardiovascular Diabetology, Vol 21, Iss 1, Pp 1-10 (2022)

مصطلحات موضوعية: Coronavirus 2019 (COVID-19), Type 1 diabetes, Type 2 diabetes, Mortality, Cardiovascular complications, Diseases of the circulatory (Cardiovascular) system, RC666-701

الوصف: Abstract Background The risk of severe coronavirus disease 2019 (COVID-19) is increased in people with diabetes, but effects of diabetes type and other risk factors remain incompletely characterized. We studied this in a Swedish cohort of hospitalized patients with type 1 and type 2 diabetes (T1D and T2D), also including comparisons with influenza epidemics of recent years. Methods Nationwide healthcare registries were used to identify patients. A total of 11,005 adult patients with diabetes (T1D, n = 373; T2D, n = 10,632) were hospitalized due to COVID-19 from January 1, 2020 to September 1, 2021. Moreover, 5111 patients with diabetes (304 T1D, 4807 T2D) were hospitalized due to influenza from January 1, 2015 to December 31, 2019. Main outcomes were death within 28 days after admission and new hospitalizations for heart failure (HF), chronic kidney disease (CKD), cardiorenal disease (CRD; composite of HF and CKD), myocardial infarction (MI) and stroke during 1 year of follow-up. Results Number of deaths and CRD events were 2025 and 442 with COVID-19 and 259 and 525 with influenza, respectively. Age- and sex-adjusted Cox regression models in COVID-19 showed higher risk of death and HF in T1D vs. T2D, hazard ratio (HR) 1.77 (95% confidence interval 1.41–2.22) and 2.57 (1.31–5.05). With influenza, T1D was associated with higher risk of death compared with T2D, HR 1.80 (1.26–2.57). Older age and previous CRD were associated with higher risks of death and hospitalization for CRD. After adjustment for prior comorbidities, mortality differences were still significant, but there were no significant differences in cardiovascular and renal outcomes. COVID-19 relative to influenza was associated with higher risk of death in both T1D and T2D, HR 2.44 (1.60–3.72) and 2.81 (2.59–3.06), respectively. Conclusions In Sweden, patients with T1D as compared to T2D had a higher age- and sex-adjusted risk of death within 28 days and HF within one year after COVID-19 hospitalization, whereas the risks of other non-fatal cardiovascular and renal disease events were similar. Patients with T1D as well as T2D have a greater mortality rate when hospitalized due to COVID-19 compared to influenza, underscoring the importance of vaccination and other preventive measures against COVID-19 for diabetes patients.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1475-2840Test

الوصول الحر: https://doaj.org/article/61935048b5c849f9af4bf5454f20c99fTest

المؤلفون: Giovanni Fanni, Jan W. Eriksson, Maria J. Pereira

المصدر: Metabolites, Vol 13, Iss 1, p 131 (2023)

مصطلحات موضوعية: type 2 diabetes, oral glucose tolerance test, metabolomics, Microbiology, QR1-502

الوصف: Metabolic inflexibility is a hallmark of insulin resistance and can be extensively explored with high-throughput metabolomics techniques. However, the dynamic regulation of the metabolome during an oral glucose tolerance test (OGTT) in subjects with type 2 diabetes (T2D) is largely unknown. We aimed to identify alterations in metabolite responses to OGTT in subjects with T2D using untargeted metabolomics of both plasma and subcutaneous adipose tissue (SAT) samples. Twenty subjects with T2D and twenty healthy controls matched for sex, age, and body mass index (BMI) were profiled with untargeted metabolomics both in plasma (755 metabolites) and in the SAT (588) during an OGTT. We assessed metabolite concentration changes 90 min after the glucose load, and those responses were compared between patients with T2D and controls. Post-hoc analyses were performed to explore the associations between glucose-induced metabolite responses and markers of obesity and glucose metabolism, sex, and age. During the OGTT, T2D subjects had an impaired reduction in plasma levels of several metabolite families, including acylcarnitines, amino acids, acyl ethanolamines, and fatty acid derivates (p < 0.05), compared to controls. Additionally, patients with T2D had a greater increase in plasma glucose and fructose levels during the OGTT compared to controls (p < 0.05). The plasma concentration change of most metabolites after the glucose load was mainly associated with indices of hyperglycemia rather than insulin resistance, insulin secretion, or BMI. In multiple linear regression analyses, hyperglycemia indices (glucose area under the curve (AUC) during OGTT and glycosylated hemoglobin (HbA1c)) were the strongest predictors of plasma metabolite changes during the OGTT. No differences were found in the adipose tissue metabolome in response to the glucose challenge between T2D and controls. Using a metabolomics approach, we show that T2D patients display attenuated responses in several circulating metabolite families during an OGTT. Besides the well-known increase in monosaccharides, the glucose-induced lowering of amino acids, acylcarnitines, and fatty acid derivatives was attenuated in T2D subjects compared to controls. These data support the hypothesis of inflexibility in several metabolic pathways, which may contribute to dysregulated substrate partitioning and turnover in T2D. These findings are not directly associated with changes in adipose tissue metabolism; therefore, other tissues, such as muscle and liver, are probably of greater importance.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2218-1989/13/1/131Test; https://doaj.org/toc/2218-1989Test

الوصول الحر: https://doaj.org/article/f1f669ef605a4fa09c9fb93c75e4e09fTest

المؤلفون: Petros Katsogiannos, Eva Randell, Magnus Sundbom, Andreas Rosenblad, Jan W. Eriksson, Janeth Leksell

المصدر: Diabetology & Metabolic Syndrome, Vol 12, Iss 1, Pp 1-8 (2020)

مصطلحات موضوعية: RYGB, Quality of life, Type 2 diabetes, Nutritional diseases. Deficiency diseases, RC620-627

الوصف: Abstract Background To examine the effects of gastric bypass surgery on health-related quality of life (HRQoL) in obese patients with type 2 diabetes, and to investigate their experiences of life adjustments using quantitative and qualitative methods. Methods Thirteen patients with type 2 diabetes and obesity, (body mass index, BMI > 30 kg/m2), participating in a randomized clinical trial, completed this sub-study. HRQoL was evaluated before, and at 6 months and 2 years after gastric bypass surgery, using the RAND- 36-item health survey. At 2 years, interviews for in-depth analysis of HRQoL changes were performed. Results Significant improvement was observed from baseline to 6 months for 2 of the eight health concepts, general health, and emotional well-being. At 2 years, improvements were also seen in physical functioning, energy/fatigue, as well as sustained improvements in general health and emotional well-being. Multiple regression analyses showed mostly non-significant associations between the magnitude of decrease in weight, BMI, and HbA1c during follow-up and improvement in HRQoL. The analyses from qualitative interviews supported a common latent theme “Finding a balance between the experience of the new body weight and self-confidence”. Conclusions The improved HRQoL after gastric bypass surgery in obese patients with type 2 diabetes was not explained specifically by the magnitude of weight loss, but rather by the participants achieving a state of union between body and consciousness. Trial registration ClinicalTrials.gov Identifier NCT02729246. Date of registration 6 April 2016 – Retrospectively registered https://clinicaltrials.gov/ct2/show/NCT02729246?term=bariglykos&draw=2&rank=1Test

وصف الملف: electronic resource

العلاقة: http://link.springer.com/article/10.1186/s13098-020-00597-1Test; https://doaj.org/toc/1758-5996Test

الوصول الحر: https://doaj.org/article/88cef272bb284d698d6e859fedf42644Test

المؤلفون: Assel Sarsenbayeva, Bipasha Nandi Jui, Giovanni Fanni, Pedro Barbosa, Fozia Ahmed, Robin Kristófi, Jing Cen, Azazul Chowdhury, Stanko Skrtic, Peter Bergsten, Tove Fall, Jan W. Eriksson, Maria J. Pereira

المصدر: Metabolites, Vol 11, Iss 9, p 574 (2021)

مصطلحات موضوعية: statins, adipose tissue, β-cell, insulin resistance, glucose uptake, type 2 diabetes, Microbiology, QR1-502

الوصف: Inhibition of 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase is associated with an increased risk of new-onset type 2 diabetes. We studied the association of genetic or pharmacological HMG-CoA reductase inhibition with plasma and adipose tissue (AT) metabolome and AT metabolic pathways. We also investigated the effects of statin-mediated pharmacological inhibition of HMG-CoA reductase on systemic insulin sensitivity by measuring the HOMA-IR index in subjects with or without statin therapy. The direct effects of simvastatin (20–250 nM) or its active metabolite simvastatin hydroxy acid (SA) (8–30 nM) were investigated on human adipocyte glucose uptake, lipolysis, and differentiation and pancreatic insulin secretion. We observed that the LDL-lowering HMGCR rs12916-T allele was negatively associated with plasma phosphatidylcholines and sphingomyelins, and HMGCR expression in AT was correlated with various metabolic and mitochondrial pathways. Clinical data showed that statin treatment was associated with HOMA-IR index after adjustment for age, sex, BMI, HbA1c, LDL-c levels, and diabetes status in the subjects. Supra-therapeutic concentrations of simvastatin reduced glucose uptake in adipocytes and normalized fatty acid-induced insulin hypersecretion from β-cells. Our data suggest that inhibition of HMG-CoA reductase is associated with insulin resistance. However, statins have a very mild direct effect on AT and pancreas, hence, other tissues as the liver or muscle appear to be of greater importance.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2218-1989/11/9/574Test; https://doaj.org/toc/2218-1989Test

الوصول الحر: https://doaj.org/article/7fa54f4ef2d6451783b2294999d68808Test

المؤلفون: Fozia Ahmed, Susanne Hetty, Milica Vranic, Giovanni Fanni, Joel Kullberg, Maria João Pereira, Jan W Eriksson

المصدر: Adipocyte. 11:434-447

مصطلحات موضوعية: obesity, Histology, CRISPR, insulin resistance, lipid metabolism, Endokrinologi och diabetes, Adipocytes, type 2 diabetes, Cell Biology, Endocrinology and Diabetes, cas9, adipogenesis

الوصف: Oestrogen receptor 2 (ESR2) expression has been shown to be higher in subcutaneous adipose tissue (SAT) from postmenopausal compared to premenopausal women. The functional significance of altered ESR2 expression is not fully known. This study investigates the role of ESR2 for adipose tissue lipid and glucose metabolism. SAT biopsies were obtained from 44 female subjects with or without T2D. Gene expression of ESR2 and markers of adipose function and metabolism was assessed. ESR2 knockdown was performed using CRISPR/Cas9 in preadipocytes isolated from SAT of females, and differentiation rate, lipid storage, and glucose uptake were measured. ESR2 expression was inversely correlated with measures of central obesity and expression of some fatty acid oxidation markers, and positively correlated with lipid storage and glucose transport markers. Differentiation was reduced in ESR2 knockdown preadipocytes. This corresponded to reduced expression of markers of differentiation and lipogenesis. Glucose uptake was reduced in knockdown adipocytes. Our results indicate that ESR2 deficiency in women is associated with visceral adiposity and impaired subcutaneous adipocyte differentiation as well as glucose and lipid utilization. High ESR2 expression, as seen after menopause, could be a contributing factor to SAT expansion. This may support a possible target to promote a healthy obesity phenotype.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b32017d0441159cb5d0d1b3eb6eb13b5Test
https://doi.org/10.1080/21623945.2022.2102116Test

المؤلفون: Jan W. Eriksson, Björn Eliasson, Louise Bennet, Johan Sundström

المصدر: Diabetologia. 65:1575-1586

مصطلحات موضوعية: Randomised trial, Microvascular complications, Endocrinology, Diabetes and Metabolism, First-line treatment, Type 2 diabetes, Review, Endocrinology and Diabetes, Diabetes Mellitus, Type 2, Clinical outcomes, Endokrinologi och diabetes, Internal Medicine, Humans, Hypoglycemic Agents, Registries, Glucose-lowering drugs, Healthcare registry, Mortality, Macrovascular complications

الوصف: This narrative review describes a new approach to navigation in a challenging landscape of clinical drug development in diabetes. Successful outcome studies in recent years have led to new indications and guidelines in type 2 diabetes, yet the number of clinical trials in diabetes is now declining. This is due to many environmental factors acting in concert, including the prioritisation of funding for other diseases, high costs of large randomised clinical trials, increase in regulatory requirements and limited entry of novel candidate drugs. There is a need for novel and cost-effective paradigms of clinical development to meet these and other challenges. The concept of registry-based randomised clinical trials (RRCTs) is an attractive option. In this review we focus on type 2 diabetes and the prevention of cardiovascular and microvascular comorbidities and mortality, using the Swedish SMARTEST trial as an example of an RRCT. We also give some examples from other disease areas. The RRCT concept is a novel, cost-effective and scientifically sound approach for conducting large-scale diabetes trials in a real-world setting. Graphical abstract

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::07795f466245602230e3214e0f5758adTest
https://doi.org/10.1007/s00125-022-05762-xTest

المؤلفون: Fozia Ahmed, Prasad G Kamble, Susanne Hetty, Giovanni Fanni, Milica Vranic, Assel Sarsenbayeva, Robin Kristófi, Kristina Almby, Maria K Svensson, Maria J Pereira, Jan W Eriksson

المصدر: The Journal of Clinical Endocrinology & Metabolism. 107:e1879-e1889

مصطلحات موضوعية: Endocrinology, Diabetes and Metabolism, Biochemistry (medical), Clinical Biochemistry, Estrogen Receptor alpha, menopause, Reproduktionsmedicin och gynekologi, Estrogens, Endocrinology and Diabetes, Polymorphism, Single Nucleotide, Biochemistry, adipose tissue, Postmenopause, Cholesterol, Glucose, Endocrinology, Adipose Tissue, Diabetes Mellitus, Type 2, Receptors, Estrogen, estradiol, insulin resistance, Obstetrics, Gynecology and Reproductive Medicine, Endokrinologi och diabetes, Humans, Female, type 2 diabetes

الوصف: Context Reduced estrogen levels in postmenopausal women predispose them to metabolic side effects, including insulin resistance and type 2 diabetes; however, the cellular mechanisms are not well understood. Objective This work aimed to study the expression of estrogen receptors in adipose tissue from pre- and postmenopausal women and the effects of estradiol (E2) on glucose uptake of adipocytes. Methods Subcutaneous (SAT) and visceral adipose tissue (VAT) obtained from pre- and postmenopausal women (19-51 and 46-75 years old, respectively) were used to measure gene expression of ESR1 and ESR2. SAT tissue was incubated with E2, and glucose uptake and estrogen receptor levels were measured. Polymorphisms in ESR1 and ESR2 were addressed in public databases to identify single nucleotide polymorphisms associated with metabolic traits. Results ESR2 expression was lower in pre- vs postmenopausal women, corresponding to lower ESR1:ESR2 gene expression ratio in postmenopausal women. In premenopausal women, the expression of ESR1 was higher in VAT than in SAT. In both pre- and postmenopausal women, ESR2 expression was lower in VAT than in SAT. In late, but not pre- or early postmenopausal women, E2 reduced glucose uptake and GLUT4 protein and increased expression of ESR2. ESR1 polymorphisms were associated with weight, body fat distribution, and total cholesterol, and ESR2 polymorphisms were associated with total cholesterol and triglyceride levels and with body fat percentage. Conclusion E2 inhibits glucose utilization in human adipocytes in late postmenopausal women. Changes in glucose utilization over time since menopause may be explained by a lower ESR1:ESR2 ratio. This can have clinical implications on the timing of estrogen treatment in postmenopausal women.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::53fd447fd508411eb0fc65121b353bd5Test
https://doi.org/10.1210/clinem/dgac042Test

المؤلفون: Jan W. Eriksson, Robin Kristófi

المصدر: Journal of Endocrinology. 251:R11-R22

مصطلحات موضوعية: Blood Glucose, Drug, medicine.medical_specialty, medicine.drug_class, Endocrinology, Diabetes and Metabolism, media_common.quotation_subject, Type 2 diabetes, Pharmacology, Endocrinology, Diabetes mellitus, Internal medicine, medicine, Animals, Humans, Hypoglycemic Agents, PI3K/AKT/mTOR pathway, media_common, Inflammation, business.industry, Biguanide, Clinical Studies as Topic, medicine.disease, Metformin, Mitochondrial respiratory chain, Gluconeogenesis, business, medicine.drug

الوصف: Metformin is a biguanide drug widely used as the initial treatment of type 2 diabetes. Despite its widespread use, its precise mechanisms of action remain incompletely characterised. Its effect in lowering blood glucose is largely related to the suppression of gluconeogenesis in the liver, which is probably accomplished by partial inhibition of the mitochondrial respiratory chain complex 1 with a subsequent increase in intracellular AMP levels and activation of AMP kinase. Several local and systemic anti-inflammatory effects of metformin have been described. Many of these effects seem to be mediated by AMP kinase activation and downstream effects inhibiting mTOR and NF-κB pro-inflammatory signalling cascades. However, there are also studies describing actions independent of AMP kinase action. In this review, we summarise the currently known mechanisms of metformin on inflammatory pathways and the clinical evidence underpinning the use of metformin as a potential anti-inflammatory drug.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b47f77aba0efa329b2e4456cf0d145b4Test
https://doi.org/10.1530/joe-21-0194Test

المؤلفون: Maria J. Pereira, Martin Lundqvist, Mark Lubberink, Robin Visvanathar, Stanko Skrtic, Robin Strand, Jan W. Eriksson, Petros Katsogiannos, Håkan Ahlström, Simon Ekström, Joel Kullberg

المصدر: European Journal of Endocrinology. 184:879-889

مصطلحات موضوعية: Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Glucose uptake, 030209 endocrinology & metabolism, Type 2 diabetes, Carbohydrate metabolism, Multimodal Imaging, Prediabetic State, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Insulin resistance, Hyperinsulinism, Internal medicine, Diabetes mellitus, Hyperinsulinemia, Humans, Medicine, Prediabetes, Muscle, Skeletal, Aged, business.industry, General Medicine, Middle Aged, Glucose clamp technique, medicine.disease, Magnetic Resonance Imaging, Glucose, Adipose Tissue, Diabetes Mellitus, Type 2, Positron-Emission Tomography, 030220 oncology & carcinogenesis, Glucose Clamp Technique, Female, Insulin Resistance, business

الوصف: Objective To obtain direct quantifications of glucose turnover, volumes and fat content of several tissues in the development of type 2 diabetes (T2D) using a novel integrated approach for whole-body imaging. Design and methods Hyperinsulinemic–euglycemic clamps and simultaneous whole-body integrated [18F]FDG-PET/MRI with automated analyses were performed in control (n = 12), prediabetes (n = 16) and T2D (n = 13) subjects matched for age, sex and BMI. Results Whole-body glucose uptake (Rd) was reduced by approximately 25% in T2D vs control subjects, and partitioning to brain was increased from 3.8% of total Rd in controls to 7.1% in T2D. In liver, subcutaneous AT, thigh muscle, total tissue glucose metabolic rates (MRglu) and their % of total Rd were reduced in T2D compared to control subjects. The prediabetes group had intermediate findings. Total MRglu in heart, visceral AT, gluteus and calf muscle was similar across groups. Whole-body insulin sensitivity assessed as glucose infusion rate correlated with liver MRglu but inversely with brain MRglu. Liver fat content correlated with MRglu in brain but inversely with MRglu in other tissues. Calf muscle fat was inversely associated with MRglu only in the same muscle group. Conclusions This integrated imaging approach provides detailed quantification of tissue-specific glucose metabolism. During T2D development, insulin-stimulated glucose disposal is impaired and increasingly shifted away from muscle, liver and fat toward the brain. Altered glucose handling in the brain and liver fat accumulation may aggravate insulin resistance in several organs.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bde5cf34d3ff204657a9980524d43761Test
https://doi.org/10.1530/eje-20-1359Test

المؤلفون: Maria J Pereira, Ayesha Azim, Susanne Hetty, Bipasha Nandi Jui, Joel Kullberg, Martin H Lundqvist, Jan W Eriksson

المصدر: Cytokine. 161

مصطلحات موضوعية: Inflammation, Glucose uptake, Immunology, Adipose tissue, Type 2 diabetes, Hematology, Endocrinology and Diabetes, Interleukin-33, Biochemistry, Lipids, Glucose, Diabetes Mellitus, Type 2, Adipose Tissue, Endokrinologi och diabetes, IL-33, Adipocytes, Immunology and Allergy, Humans, Obesity, RNA, Messenger, Insulin Resistance, Molecular Biology

الوصف: OBJECTIVE: Interleukin-33 (IL-33) is associated with obesity-related inflammation. We aim to investigate IL-33 expression in subcutaneous adipose tissue (SAT) in type 2 diabetes (T2D) subjects and its effects on human adipocyte glucose uptake. METHODS: Expression of IL-33 was analysed in SAT from cohort studies including subjects with and without obesity and T2D and correlated with insulin resistance and obesity markers. Magnetic resonance imaging (MRI) of tissue fat volumes was performed. We investigated the effects of IL-33 treatment on ex vivo adipocyte glucose uptake. RESULTS: T2D subjects had higher IL-33 gene and protein expression in SAT than the control subjects. IL-33 mRNA expression was positively correlated with markers of dysglycemia (e.g. HbA1c), insulin resistance (e.g. HOMA-IR) and adiposity (BMI, visceral adipose tissue volume, liver and pancreas fat %). In multiple linear regression analyses, insulin resistance and T2D status were the strongest predictors of IL-33, independent of BMI. IL-33 mRNA expression was negatively correlated with expression of genes regulating adipocyte glucose uptake, lipid storage, and adipogenesis (e.g.glucose transporter 1 and 4 (GLUT1/4), fatty acid binding protein 4 (FABP4), and PPARG). Additionally, incubation of SAT with IL-33 reduced adipocyte glucose uptake and GLUT4 gene and protein expression. CONCLUSIONS: Our findings suggest that T2D subjects have higher IL-33 gene and protein expressionin SATthan control subjects, which is associated with insulin resistance and reduced gene expression of lipid storage and adipogenesis markers. IL-33 may reduce adipocyte glucose uptake. This opens up a potential pharmacological route for reversing insulin resistance in T2D and prediabetes.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::738881e9fad66ffab8c67193eb2bb95eTest
https://pubmed.ncbi.nlm.nih.gov/36368230Test